Influence of posture on pharmacokinetics.
BACKGROUND
Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion).


OBJECTIVE
Based on a systematic literature search, current data on the effect of posture on physiological characteristics and/or pharmacokinetics are summarized, and the relevance of possible effects, such as those presenting in clinical practice and clinical pharmacokinetic studies, is assessed.


RESULTS
Postures which favour rapid gastric emptying (sitting, standing, recumbent right) accelerate the absorption of orally administered drugs. Consequently, these postures favour a shorter time to reach peak plasma drug concentration (t(max)) and a higher maximum plasma drug concentration (C(max)) and--in the case of transient saturation of first-pass metabolism--total exposure (area under the concentration-time curve, AUC) in comparison to recumbent left and supine positions (e.g. nifedipine: AUC 30 and 38% higher in standing and right lateral position vs. left lateral position; C(max) 149 and 80% higher, respectively). The magnitude of these postural effects depends strongly on the nature and amount of liquids and food ingested before drug administration and is most pronounced in the fasting state and after administration with a nonnutrient liquid. Changes in splanchnic-hepatic blood flow (e.g. reduction of estimated hepatic perfusion by 37% in standing vs. supine position) may substantially affect the metabolism of orally administered drugs, especially of those with a high/saturable first-pass metabolism. For highly protein-bound drugs (e.g. phenytoin, imipramine), the total plasma concentration has been found to be approximately 10% higher in standing than lying subjects due to changes in plasma volume.


CONCLUSIONS
Positioning of a patient may be an effective method of enhancing or retarding absorption of some drugs in appropriate clinical situations (e.g. toxic ingestions, bedridden patients). In clinical pharmacokinetic trials, such as bioequivalence studies, defining and maintaining posture precisely is a useful approach for reducing within- and between-subject variability.
Queckenberg
Christian
C
Department of Pharmacology, Clinical Pharmacology, University Hospital, University of Cologne, Cologne, Germany. christian.queckenberg@uk-koeln.de
Fuhr
Uwe
U
D000284:Administration, Oral; D019540:Area Under Curve; D002986:Clinical Trials as Topic; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010599:Pharmacokinetics; D011187:Posture / Q000502:physiology*; D013997:Time Factors
D004364:Pharmaceutical Preparations